tbuckley/cabot-search huggingface dataset:
Implantable Defibrillator System Shock Function, Mortality, and Cause of Death After Magnetic Resonance Imaging
Authors: Joshua Ra, Matt T. Oberdier, Masahito Suzuki, Dhananjay Vaidya, Yisi Liu, Rozann Hansford, Diana McVeigh, Valeria Weltin, Susumu Tao, David R. Thiemann, Saman Nazarian, Henry R. Halperin
Journal: Annals of Internal Medicine (2023)

Background: Studies have shown that magnetic resonance imaging (MRI) does not have clinically important effects on the device parameters of non–MRI-conditional implantable cardioverter-defibrillators (ICDs). However, data on non–MRI-conditional ICD detection and treatment of arrhythmias after MRI are limited. Objective: To examine if non–MRI-conditional ICDs have preserved shock function of arrhythmias after MRI. Design: Prospective cohort study. (ClinicalTrials.gov: NCT01130896) Setting: 1 center in the United States. Patients: 629 patients with non–MRI-conditional ICDs enrolled consecutively between February 2003 and January 2015. Interventions: 813 total MRI examinations at a magnetic field strength of 1.5 Tesla using a prespecified safety protocol. Measurements: Implantable cardioverter-defibrillator interrogations were collected after MRI. Clinical outcomes included arrhythmia detection and treatment, generator or lead exchanges, adverse events, and death. Results: During a median follow-up of 2.2 years from MRI to latest available ICD interrogation before generator or lead exchange in 536 patients, 4177 arrhythmia episodes were detected, and 97 patients received ICD shocks. Sixty-one patients (10% of total) had 130 spontaneous ventricular tachycardia or fibrillation events terminated by ICD shocks. A total of 210 patients (33% of total) are known to have died (median, 1.7 years from MRI to death); 3 had cardiac arrhythmia deaths where shocks were indicated without direct evidence of device dysfunction. Limitations: Data were acquired at a single center and may not be generalizable to other clinical settings and MRI facilities. Implantable cardioverter-defibrillator interrogations were not available for a subset of patients; adjudication of cause of death relied solely on death certificate data in a subset. Conclusion: Non–MRI-conditional ICDs appropriately treated detected tachyarrhythmias after MRI. No serious adverse effects on device function were reported after MRI. Primary Funding Source: Johns Hopkins University and National Institutes of Health.
Technical Innovation in Critical Care in a World of Constraints: Lessons from the COVID-19 Pandemic
Authors: Armand Mekontso Dessap, Jean-Christophe Marie Richard, Tim Baker, Aurélie Godard, Guillaume Carteaux
Journal: American Journal of Respiratory and Critical Care Medicine (2023)

The COVID-19 crisis was characterized by a massive need for respiratory support, which has unfortunately not been met globally. This situation mimicked those which gave rise to critical care in the past. Since the polio epidemic in the 50's, the technological evolution of respiratory support has enabled health professionals to save the lives of critically-ill patients worldwide every year. However, much of the current innovation work has turned around developing sophisticated, complex, and high-cost standards and approaches whose resilience is still questionable upon facing constrained environments or contexts, as seen in resuscitation work outside intensive care units, during pandemics, or in low-income countries. Ventilatory support is an essential life-saving tool for patients with respiratory distress. It requires an oxygen source combined to a ventilatory assistance device, an adequate monitoring system, and properly trained caregivers to operate it. Each of these elements can be subject to critical constraints, which we can no longer ignore. The innovation process should incorporate them as a prima materia, whilst focusing on the core need of the field using the concept of frugal innovation. Having a universal access to oxygen and respiratory support, irrespective of the context and constraints, necessitates: i) developing cost-effective, energy-efficient, and maintenance-free oxygen generation devices; ii) improving the design of non-invasive respiratory devices (for example, with oxygen saving properties); iii) conceiving fully frugal ventilators and universal monitoring systems; iv) broadening ventilation expertise by developing end-user training programs in ventilator assistance. The frugal innovation approach may give rise to a more resilient and inclusive critical care system. This paradigm shift is essential for the current and future challenges.
Adjuvant Chemotherapy in Older Women With Early Breast Cancer
Authors: Dario Trapani
Journal: Journal of Clinical Oncology (2023)

The Oncology Grand Rounds series is designed to place original reports published in the Journal into clinical context. A case presentation is followed by a description of diagnostic and management challenges, a review of the relevant literature, and a summary of the authors’ suggested management approaches. The goal of this series is to help readers better understand how to apply the results of key studies, including those published in Journal of Clinical Oncology , to patients seen in their own clinical practice. The clinical discussion on the adjuvant chemotherapy in older patients with breast cancer (BC) should routinely include comprehensive considerations of the health implications of competitive comorbidities, the safety of the treatment itself, and the likelihood that an appropriate dose intensity will be received (ie, relative dose intensity &gt; 85%). All these factors have prognostic implications, as recently confirmed in the secondary analysis of the Hurria Older PatiEnts clinical trial. Full-informed, shared decision making is essential to provide best care. Our clinical approach for women with BC age ≥ 65 years is based on a standardized screening for frailty, triggering comprehensive geriatric assessment, as appropriate. We only recommend evidence-based regimens that have showed to reduce the risk of cancer recurrence and potentially increase overall survival. We frequently prefer docetaxel-cyclophosphamide, for hormone receptor–positive BC, on the basis of the subgroup analysis of the USOR-9735 study in older population. We avoid single agents (eg, capecitabine or weekly docetaxel), as showed to be inferior treatments in the CALGB-49907 and ELDA trials, and modified nonstandard regimens, for the lack of strong evidence in support.
Efficacy and Safety of Mirvetuximab Soravtansine in Patients With Platinum-Resistant Ovarian Cancer With High Folate Receptor Alpha Expression: Results From the SORAYA Study
Authors: Ursula A. Matulonis, Domenica Lorusso, Ana Oaknin, Sandro Pignata, Andrew Dean, Hannelore Denys, Nicoletta Colombo, Toon Van Gorp, Jason A. Konner, Margarita Romeo Marin, Philipp Harter, Conleth G. Murphy, Jiuzhou Wang, Elizabeth Noble, Brooke Esteves, Michael Method, Robert L. Coleman
Journal: Journal of Clinical Oncology (2023)

PURPOSE Single-agent chemotherapies have limited activity and considerable toxicity in patients with platinum-resistant epithelial ovarian cancer (PROC). Mirvetuximab soravtansine (MIRV) is an antibody-drug conjugate targeting folate receptor α (FRα). SORAYA is a single-arm, phase II study evaluating efficacy and safety of MIRV in patients with PROC. METHODS SORAYA enrolled FRα-high patients with PROC who had received one to three prior therapies, including required bevacizumab. The primary end point was confirmed objective response rate (ORR) by investigator; duration of response was the key secondary end point. RESULTS One hundred six patients were enrolled; 105 were evaluable for efficacy. All patients had received prior bevacizumab, 51% had three prior lines of therapy, and 48% received a prior poly ADP-ribose polymerase inhibitor. Median follow-up was 13.4 months. ORR was 32.4% (95% CI, 23.6 to 42.2), including five complete and 29 partial responses. The median duration of response was 6.9 months (95% CI, 5.6 to 9.7). In patients with one to two priors, the ORR by investigator was 35.3% (95% CI, 22.4 to 49.9) and in patients with three priors was 30.2% (95% CI, 18.3 to 44.3). The ORR by investigator was 38.0% (95% CI, 24.7 to 52.8) in patients with prior poly ADP-ribose polymerase inhibitor exposure and 27.5% (95% CI, 15.9 to 41.7) in those without. The most common treatment-related adverse events (all grade and grade 3-4) were blurred vision (41% and 6%), keratopathy (29% and 9%), and nausea (29% and 0%). Treatment-related adverse events led to dose delays, reductions, and discontinuations in 33%, 20%, and 9% of patients, respectively. CONCLUSION MIRV demonstrated consistent clinically meaningful antitumor activity and favorable tolerability and safety in patients with FRα-high PROC who had received up to three prior therapies, including bevacizumab, representing an important advance for this biomarker-selected population.
Cardiovascular Complications of Down Syndrome: Scoping Review and Expert Consensus
Authors: Konstantinos Dimopoulos, Andrew Constantine, Paul Clift, Robin Condliffe, Shahin Moledina, Katrijn Jansen, Ryo Inuzuka, Gruschen R. Veldtman, Clifford L. Cua, Edgar Lik Wui Tay, Alexander R. Opotowsky, George Giannakoulas, Rafael Alonso-Gonzalez, Rachael Cordina, George Capone, Judith Namuyonga, Charmaine H. Scott, Michele D’Alto, Francisco J. Gamero, Brian Chicoine, Hong Gu, Alisa Limsuwan, Tosin Majekodunmi, Werner Budts, Gerry Coghlan, Craig S. Broberg, Konstantinos Dimopoulos, Andrew Constantine, Paul Clift, Robin Condliffe, Shahin Moledina, Katrijn Jansen
Journal: Circulation (2023)

Cardiovascular disease is a leading cause of morbidity and mortality in individuals with Down syndrome. Congenital heart disease is the most common cardiovascular condition in this group, present in up to 50% of people with Down syndrome and contributing to poor outcomes. Additional factors contributing to cardiovascular outcomes include pulmonary hypertension; coexistent pulmonary, endocrine, and metabolic diseases; and risk factors for atherosclerotic disease. Moreover, disparities in the cardiovascular care of people with Down syndrome compared with the general population, which vary across different geographies and health care systems, further contribute to cardiovascular mortality; this issue is often overlooked by the wider medical community. This review focuses on the diagnosis, prevalence, and management of cardiovascular disease encountered in people with Down syndrome and summarizes available evidence in 10 key areas relating to Down syndrome and cardiac disease, from prenatal diagnosis to disparities in care in areas of differing resource availability. All specialists and nonspecialist clinicians providing care for people with Down syndrome should be aware of best clinical practice in all aspects of care of this distinct population.
Pertuzumab, Trastuzumab, and an Aromatase Inhibitor for HER2-Positive and Hormone Receptor–Positive Metastatic or Locally Advanced Breast Cancer: PERTAIN Final Analysis
Authors: Grazia Arpino, Juan de la Haba Rodríguez, Jean-Marc Ferrero, Sabino De Placido, C. Kent Osborne, Dirk Klingbiel, Valentine Revelant, Christine Wohlfarth, Raf Poppe, Mothaffar F. Rimawi
Journal: Clinical Cancer Research (2023)

Abstract Purpose: In PERTAIN's primary analysis (31 months’ median follow-up), adding pertuzumab to trastuzumab and an aromatase inhibitor (AI) with/without chemotherapy significantly improved progression-free survival (PFS) in patients with previously untreated HER2-positive and hormone receptor–positive metastatic or locally advanced breast cancer (M/LABC). A potentially enhanced treatment effect was observed in patients with no induction chemotherapy. We present the final analysis (&amp;gt;6 years’ median follow-up). Patients and Methods: Patients (N = 258) were randomized 1:1 to pertuzumab (loading/maintenance: 840/420 mg) plus trastuzumab (loading/maintenance: 8/6 mg/kg) every 3 weeks and an AI (1 mg anastrozole or 2.5 mg letrozole daily; Arm A), or trastuzumab and an AI (Arm B). Induction chemotherapy was at investigator discretion. Primary endpoint: PFS. Key secondary endpoints: overall survival (OS) and safety. Results: Median PFS was 20.6 versus 15.8 months in Arms A and B, respectively (stratified HR, 0.67; P = 0.006). Median OS was 60.2 versus 57.2 months (stratified HR, 1.05; P = 0.78). Pertuzumab treatment effect was potentially enhanced in patients with no induction chemotherapy (26.6 vs. 12.5 months). Any-grade adverse events (AE) occurred in 122 patients per arm (96.1% vs. 98.4%); grade ≥ 3 AEs in 72 (56.7%) and 51 (41.1%); serious AEs in 46 (36.2%) and 28 (22.6%). Conclusions: The PFS benefit of pertuzumab was maintained and OS was similar between arms at final analysis. Adding pertuzumab may enhance activity in patients who do not require first-line chemotherapy for M/LABC. No new safety concerns were reported. These data provide additional evidence of the role of first-line pertuzumab and trastuzumab in HER2-positive M/LABC.
CEACAM1 Marks Highly Suppressive Intratumoral Regulatory T Cells for Targeted Depletion Therapy
Authors: Seung Hyuck Jeon, Minyong Kang, Minwoo Jeon, Youseung Chung, A Reum Kim, Yong Joon Lee, Eui-Soon Kim, Heejin Nam, Junsik Park, Jung-Yun Lee, Eui-Cheol Shin, Seong Il Seo, Su-Hyung Park
Journal: Clinical Cancer Research (2023)

Abstract Purpose: Regulatory T cells (Tregs) exert immunosuppressive functions and hamper antitumor immune responses in the tumor microenvironment. Understanding the heterogeneity of intratumoral Tregs, and how it changes with tumor progression, will provide clues regarding novel target molecules of Treg-directed therapies. Experimental Design: From 42 patients with renal cell carcinoma and 5 patients with ovarian cancer, immune cells from tumor and peripheral blood were isolated. We performed multicolor flow cytometry and RNA-sequencing to characterize the phenotypes and heterogeneity of intratumoral Tregs. In vitro functional assays were performed to evaluate suppressive capacity of Tregs and effect of carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1)-mediated depletion. The CT26 tumor model was used to evaluate the association between intratumoral Tregs and tumor growth, and examine the in vivo role of CEACAM1+ intratumoral Tregs on antitumor immunity. Results: We found that CEACAM1 was selectively expressed on intratumoral Tregs, whereas its expression on peripheral Tregs or other immune cells was low. The CEACAM1+ intratumoral Tregs accumulated with tumor progression, whereas the CEACAM1− subset did not. Notably, we found that CEACAM1 marked intratumoral Tregs that exhibited highly suppressive and activated phenotypes with substantial clonal expansion. Depletion of CEACAM1-expressing cells from tumor-infiltrating leukocytes led to increased effector functions of tumor-infiltrating T cells. Moreover, CEACAM1+ cell depletion further enhanced anti-PD-1–mediated reinvigoration of exhausted CD8+ T cells. Conclusions: CEACAM1 marks highly suppressive subset of intratumoral Tregs, and can be a target for selective depletion of intratumoral Tregs. These results may inform future studies on CEACAM1-mediated depletion in patients with cancer.
Impact of Patient Selection on Performance of an Early Rule-Out Pathway for Myocardial Infarction: From Research to the Real World
Authors: Anda Bularga, Kuan Ken Lee, Anoop S.V. Shah, Atul Anand, Andrew R. Chapman, Chris Tuck, David E. Newby, Sarah Jenks, Nicholas L. Mills, Dorien M. Kimenai
Journal: Circulation (2023)

arly rule-out pathways for myocardial infarction using high-sensitivity cardiac troponin are now recommended by international clinical guidelines. 1 Although developed in selected patients participating in research studies, these pathways are applied widely in clinical practice where the diagnostic performance and effectiveness may differ substantially.We previously demonstrated that the selection of patients for high-sensitivity cardiac troponin testing influences the apparent prevalence of myocardial infarction. 2 Here, we evaluated the impact of patient selection on the performance of the High-STEACS trial (High-Sensitivity Troponin in the Evaluation of Patients with Acute Coronary Syndrome) early rule-out pathway for myocardial infarction 3 in unselected consecutive patients in clinical practice and in selected patients consenting to participate in a research study.Both cohorts comprised patients with suspected acute coronary syndrome presenting to emergency departments across 3 acute-care hospitals in Scotland.An electronic form embedded in practice was used to record prospectively the indication for cardiac troponin testing, symptoms, and timing of symptom onset.In the unselected cohort, data were collected in consecutive patients as part of a service evaluation in which the usual care clinician measured cardiac troponin for suspected acute coronary syndrome between June 7, 2021, and September 8, 2021.Data collection and record linkage were performed with approval from the Caldicott Guardian and the ethics committee.In the selected cohort, patients with suspected acute coronary
<i>NPY</i> Methylated ctDNA is a Promising Biomarker for Treatment Response Monitoring in Metastatic Colorectal Cancer
Authors: Katleen Janssens, Greetje Vanhoutte, Willem Lybaert, Wim Demey, Jochen Decaestecker, Koen Hendrickx, Hassan Rezaei Kalantari, Karen Zwaenepoel, Patrick Pauwels, Erik Fransen, Ken Op de Beeck, Guy Van Camp, Christian Rolfo, Marc Peeters
Journal: Clinical Cancer Research (2023)

Abstract Purpose: Analysis of methylation markers in liquid biopsies is a promising technique for the follow-up of patients with metastatic colorectal cancer (mCRC), because they can be used in all patients, regardless of their mutational status. Therefore, we studied the value of NPY methylation analysis in circulating tumor DNA (ctDNA) for accurate response monitoring in patients with mCRC in the PANIB trial. Experimental Design: The PANIB trial was a randomized phase II trial designed to compare FOLFOX plus panitumumab and FOLFOX plus bevacizumab in patients with RAS wild-type unresectable mCRC. The results of sequential liquid biopsies were correlated with results of imaging. Results: Forty patients were included from six Belgian hospitals. Analysis of the liquid biopsies revealed that higher baseline levels of methylated ctDNA was associated with a significantly shorter overall survival [HR, 1.015; 95% confidence interval (CI), 1.005–1.025; P = 0.002]. Furthermore, 37 patients provided at least two liquid biopsies. Thirty-one of them showed a decrease in the methylation ratio after the start of therapy, which corresponded with stable disease or response on imaging at the first evaluation. When comparing the panitumumab and bevacizumab arm, significantly higher objective response and early tumor shrinkage rates were observed in the panitumumab arm (P = 0.048 and 0.015, respectively). However, due to a small study population, the trial was underpowered to detect a significant difference in survival. Conclusions: The results of this study confirm that baseline methylated ctDNA is a prognostic marker and indicate that NPY methylation is a promising marker for response monitoring in patients with mCRC.
A patient-centric modeling framework captures recovery from SARS-CoV-2 infection
Authors: Hélène Ruffieux, Aimee L. Hanson, Samantha Lodge, Nathan G. Lawler, Luke Whiley, Nicola Gray, Tui H. Nolan, Laura Bergamaschi, Federica Mescia, Lorinda Turner, Aloka de Sa, Victoria S. Pelly, Prasanti Kotagiri, Nathalie Kingston, John R. Bradley, Elaine Holmes, Julien Wist, Jeremy K. Nicholson, Paul A. Lyons, Kenneth G. C. Smith, Sylvia Richardson, Glenn R. Bantug, Christoph Hess
Journal: Nature Immunology (2023)

Abstract The biology driving individual patient responses to severe acute respiratory syndrome coronavirus 2 infection remains ill understood. Here, we developed a patient-centric framework leveraging detailed longitudinal phenotyping data and covering a year after disease onset, from 215 infected individuals with differing disease severities. Our analyses revealed distinct ‘systemic recovery’ profiles, with specific progression and resolution of the inflammatory, immune cell, metabolic and clinical responses. In particular, we found a strong inter-patient and intra-patient temporal covariation of innate immune cell numbers, kynurenine metabolites and lipid metabolites, which highlighted candidate immunologic and metabolic pathways influencing the restoration of homeostasis, the risk of death and that of long COVID. Based on these data, we identified a composite signature predictive of systemic recovery, using a joint model on cellular and molecular parameters measured soon after disease onset. New predictions can be generated using the online tool http://shiny.mrc-bsu.cam.ac.uk/apps/covid-19-systemic-recovery-prediction-app , designed to test our findings prospectively.
WESTERN EQUINE ENCEPHALOMYELITIS VIRUS IN THE BLOOD OF EXPERIMENTALLY INOCULATED CHICKENS
Authors: W. McD. Hammon, W. C. Reeves
Journal: The Journal of Experimental Medicine (1946)

1. Chickens inoculated subcutaneously with 0.2 cc. of a 10–2 to 10–7 dilution of Western equine mouse brain virus had the virus in the blood serum between the 12th and the 48th hour in most instances. The fowls showed no signs of illness. 2. Viremia could be induced regularly in chickens by inoculating subcutaneously the least amount of virus which would produce encephalitis in the mouse when inoculated by the intracerebral route. 3. Even the minimal infecting dose for a chicken led to such multiplication of the virus that it was detectable in the serum in a 10–4 dilution. Moreover, a minimal infecting dose appeared to result in a longer period of viremia than was produced by a larger dose. 4. Virus has not been found to persist for more than 3 days after inoculation in any organ of the chicken tested for it and usually it did not persist over 2 days. Antibodies were present in the blood within at least 15 days after inoculation. 5. It is concluded that chickens may serve as sources of infection for mosquitoes or other blood-sucking ectoparasites for short periods of time after the infecting bite of a similar invertebrate vector. There is no evidence that the chicken serves as a latent carrier of the virus. 6. No virus could be found in the blood of 2 inoculated calves, and virus has not been demonstrated regularly or with the same case in the blood of horses or of men, as it has in that of chickens. It seems unlikely therefore that large mammals serve frequently as sources for mosquito infection. 7. These experimental data on fowls and mammals correlate well with other epidemiological and laboratory findings, in particular with the feeding preference of the mosquitoes found infected in epidemic areas.